# Pharmaceutical Strategies for West Nile Virus in Europe, an Underrecognized Cause of Severe Disease and Mortality in Older Adults: From Supportive Care to Antiviral Development

## TL;DR

This paper reviews pharmaceutical strategies for treating West Nile Virus in older adults in Europe, highlighting the lack of specific treatments and challenges in drug development.

## Contribution

The paper proposes a framework for antiviral screening and clinical trial readiness integrated into One Health systems.

## Key findings

- Older adults are more susceptible to severe WNV disease with high mortality and long-term disability.
- Current treatments are supportive, and no licensed antiviral or vaccine exists for human use.
- Drug repurposing and host-directed therapies show potential but face challenges due to age-related changes.

## Abstract

West Nile Virus (WNV) is becoming a significant and enduring public health menace in Europe, propelled by climate changes and accelerated population aging. Most infections are asymptomatic but older adults are more prone to develop neuroinvasive disease, which is characterized by high morbidity and mortality, as well as long-term neurological disturbances and disability. To date, there is still no licensed human vaccine or specific antiviral treatment, and management is mostly supportive. This review brings together the most recent information about WNV epidemiology, pathogenesis, and clinical manifestations, with a special focus on older people in Europe. We critically analyze current and novel pharmaceutical strategies, encompassing drug repurposing, nucleoside analogues, interferon-based therapies, peptides, monoclonal antibodies, and host-directed agents, emphasizing their therapeutic potential alongside the challenges presented by age-related pharmacokinetic and immunological alterations. We also discuss some important gaps in the current evidence base, such as the frequent exclusion of older adults from clinical studies and the lack of a coordinated clinical trial infrastructure that can be quickly activated during seasonal outbreaks. Lastly, we suggest a framework that combines systematic antiviral screening with the creation of a Europe-wide network of clinical trial readiness that is built into current One Health surveillance systems.